CSF PGRN May be Associated With Postoperative Delirium After Knee Replacement in Elderly Patients: The PNDABLE Study

Author(s):  
Bin Wang ◽  
Jie Xiu Sun ◽  
He Tao ◽  
Yuan Xi Deng ◽  
Nan Ya Lin ◽  
...  

Abstract BackgroundPostoperative delirium (POD) represents a serious complication following anesthesia and surgical procedures for patients undergoing surgical intervention (1). Little is known about the mechanisms underlying similarities in the core features between postoperative delirium (POD) and progranulin (PGRN)-related cognitive disorders. We herein investigated the relationship between preoperative CSF PGRN concentration and POD occurrence in the Han Chinese patients undergoing unilateral total knee arthroplasty.MethodsWe conducted an observational, prospective, and 1:1 matched (on age older than 65, the unilateral total knee arthroplasty, American Society of Anesthesiologist’ (ASA) physical status, duration of surgery, and intraoperative bleeding) case-control study. POD cases and non-POD controls were selected from the overall cohort using Confusion Assessment Method (CAM). Delirium severity was measured by the Memorial Delirium Assessment Scale (MDAS). CSF PGRN and core biomarkers were measured by ELISA using the microplate reader. The associations of CSF PGRN levels with POD risk and CSF core biomarkers were assessed.ResultsPOD incidence was 9.7% (53/545). There were significant differences in preoperative CSF PGRN concentration between POD patients and controls (P<0.001), and CSF PGRN levels increased with age, as demonstrated by a significantly positive correlation (r=0.796, P<0.001).CSF PGRN levels to increase with CAM scores and MDAS scores, as demonstrated by significantly positive correlations (r=0.693, P<0.001; r=0.590, P<0.001). There were positive associations of CSF PGRN with T-tau (β = -0.501, P < 0.001) and P-tau (β = -0.470, P < 0.001) and negative associations of CSF PGRN with Aβ1–42 (β = -0.576, P < 0.001), Aβ1–40 (β = -0.488, P < 0.001), Aβ42/p-tau (β = -0.422, P < 0.001), and Aβ42 / T- tau (β = -0.395, P < 0.001) in POD patients. The ROC curve analysis of PGRN showed that PGRN concentrations had high diagnostic value for POD.ConclusionsCSF PGRN may be associated with the POD. Aβ pathology is associated with a decrease in CSF PGRN in the absence of tau deposition and neurodegeneration, whereas tau pathology and neurodegeneration is associated with an increase in CSF PGRN.Clinical Trial Registrationwww.clinicaltrials.gov, identifier ChiCTR2000033439.

2021 ◽  
Author(s):  
Bin Wang ◽  
Xu Lin ◽  
XiuJie Sun ◽  
Fang hao Liu ◽  
He Tao ◽  
...  

Abstract Background: Postoperative delirium (POD) represents a serious complication following anesthesia and surgical procedures for patients undergoing surgical intervention. At present, there is no effective index to predict the occurrence of POD ,so the aim of this study was to validate whether cerebrospinal fluid (CSF) PGRN could predict the occurrence of POD.Methods: We conducted a prospective nested case-control and 1:1 matched (on age, diagnosis, American Society of Anesthesiologist’ (ASA) physical status, duration of surgery, and intraoperative blood loss) study. A total of 600 Han Chinese patients over the age of 65~ 90 who underwent unilateral total knee arthroplasty were included in the PNDABLE study from June 2020 to November 2020. POD cases and non-POD controls were selected from using Confusion Assessment Method (CAM) on the first, second, third and seventh (or before discharge) postoperative days. Delirium severity was measured by the Memorial Delirium Assessment Scale (MDAS). In the six month, cognitive function was assessed with the modified Telephone Interview for Cognitive Status (TICS-m) and the World Health Organization Quality of Life brief version (WHOQOLBREF). CSF PGRN and core biomarkers were measured by ELISA using the microplate reader. The associations of CSF PGRN levels with POD risk and CSF core biomarkers (Aβ1–42, Aβ1–40 ,T-tau and P-tau)were assessed. The effect of CSF PGRN on predicting POD occurrence was evaluated with the area under the receiver operating characteristic (ROC) curve (AUC).Results: POD incidence was 9.7% (53/545). There were significant differences in preoperative CSF PGRN concentration between POD patients and non-POD (P<0.001), and CSF PGRN levels decreased with age, as demonstrated by a significantly negative correlation. CSF PGRN levels decrease with CAM scores and MDAS scores, as demonstrated by significantly negative correlations(r=-0.692, P=0.001; r=-0.435, P=0.001). There were positive associations of CSF PGRN with Aβ1–42 (β = 0.756, P < 0.001) , Aβ1–40 (β =0.637, P < 0.001) and negative associations of CSF PGRN with T-tau (β = -0.716, P < 0.001) and P-tau (β = -0.739, P < 0.001) in POD patients. The ROC curve analysis of PGRN showed that PGRN concentrations had high diagnostic value for POD.Conclusions: Aβ pathology is associated with increasing in CSF PGRN whereas Tau pathology and neurodegeneration is associated with decreasing in CSF PGRN in POD patients.CSF PGRN can predict the occurrence of POD in elderly patients.Clinical Trial Registration: www.clinicaltrials.gov, identifier ChiCTR2000033439.


Author(s):  
Shekhar Saha ◽  
Kübra Karaca ◽  
Ahmad Fawad Jebran ◽  
Narges Waezi ◽  
Katharina Ort ◽  
...  

Abstract Background Depression of cholinesterase (CHE) activity has been reported to lead to an amplified neuroinflammatory response, which clinically manifests as postoperative delirium (PD). This observational study investigates the association between CHE activity and the development of PD following elective cardiac surgery. Methods Patients with preexisting neurologic deficits or carotid artery disease as well as patients undergoing reoperations or procedures under circulatory arrest have been excluded from this study. The Mini-Mental State Examination, the Confusion Assessment Method for the Intensive Care Unit, and the Intensive Care Delirium Screening Checklist were performed at regular intervals. CHE activity was estimated pre- and postoperatively until postoperative day (POD) 5 and at discharge. Results A total of 107 patients were included. PD was diagnosed in 34 (31.8%) patients, who have been compared with those without PD. Time on ventilator, length of ICU, and hospital stay were longer in patients with PD (p = 0.001, p < 0.001, and p = 0.004, respectively). MMSE scores were lower in patients with PD (p < 0.001; p = 0.015). CHE activity on POD 1 to 4 as well as at discharge were lower in the delirium group (p = 0.041; p = 0.029; p = 0.015; p = 0.035; p = 0.028, respectively). A perioperative drop of CHE activity of more than 50% and a postoperative CHE activity below 4,800 U/L (on POD 0) were independently associated with an increased risk of development of PD (p = 0.038; p = 0.008, respectively). Conclusion In addition to the established functional tests, routine estimation of CHE activity may serve as an additional diagnostic tool allowing for the timely diagnosis and treatment of PD in cardiac surgery patients.


Author(s):  
Andrea Kirfel ◽  
Jan Menzenbach ◽  
Vera Guttenthaler ◽  
Johanna Feggeler ◽  
Andreas Mayr ◽  
...  

Abstract Background Postoperative delirium (POD) is a relevant and underdiagnosed complication after cardiac surgery that is associated with increased intensive care unit (ICU) and hospital length of stay (LOS). The aim of this subgroup study was to compare the frequency of tested POD versus the coded International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis of POD and to evaluate the influence of POD on LOS in ICU and hospital. Methods 254 elective cardiac surgery patients (mean age, 70.5 ± 6.4 years) at the University Hospital Bonn between September 2018 and October 2019 were evaluated. The endpoint tested POD was considered positive, if one of the tests Confusion Assessment Method for ICU (CAM-ICU) or Confusion Assessment Method (CAM), 4 'A's Test (4AT) or Delirium Observation Scale (DOS) was positive on one day. Results POD occurred in 127 patients (50.0%). LOS in ICU and hospital were significantly different based on presence (ICU 165.0 ± 362.7 h; Hospital 26.5 ± 26.1 days) or absence (ICU 64.5 ± 79.4 h; Hospital 14.6 ± 6.7 days) of POD (p < 0.001). The multiple linear regression showed POD as an independent predictor for a prolonged LOS in ICU (48%; 95%CI 31–67%) and in hospital (64%; 95%CI 27–110%) (p < 0.001). The frequency of POD in the study participants that was coded with the ICD F05.0 and F05.8 by hospital staff was considerably lower than tests revealed by the study personnel. Conclusion Approximately 50% of elderly patients who underwent cardiac surgery developed POD, which is associated with an increased ICU and hospital LOS. Furthermore, POD is highly underdiagnosed in clinical routine.


2019 ◽  
Vol 13 (3) ◽  
pp. 133-140 ◽  
Author(s):  
Ioannis Leotsakos ◽  
Ioannis Katafigiotis ◽  
Ofer N. Gofrit ◽  
Mordechai Duvdevani ◽  
Dionysios Mitropoulos

Purpose: We aimed to thoroughly search and identify studies referring to risk factors associated with postoperative delirium (POD) in patients undergoing open as well as en-doscopic urological surgery. Methods: The review after a systematic literature search included 5 studies. Results: The incidence of POD was reported to be between 7.8 and 30% depending on the type of the urologic surgery, while in the majority of the studies the onset happened on the first postoperative day and the symptoms lasted 3 ± 0.8 days. Seventeen different risk factors for POD were identified and presented in detail. Conclusion: The Mini-Mental State Examination score and older age were significantly associated with the development of POD. However, the Confusion Assessment Method is very well validated against the diagnosis of delirium from the specialists.


Author(s):  
Layth Al Tmimi ◽  
Marc Van de Velde ◽  
Bart Meyns ◽  
Bart Meuris ◽  
Paul Sergeant ◽  
...  

AbstractBackground:To investigate the predictive value of S100 (biochemical marker of neuroglial injury) for the occurrence of postoperative delirium (POD) in patients undergoing off-pump coronary artery bypass (OPCAB)-surgery.Methods:We enrolled 92 patients older than 18 years undergoing elective OPCAB-surgery. Serum-levels of S100 were determined at baseline (BL), end of surgery (EOS) and on the first postoperative day (PD1). Postoperatively, all-patients were evaluated daily until PD5 for the presence of POD using the confusion assessment method (CAM) or the confusion assessment method for the intensive care unit (CAM-ICU) for patients in the intensive care unit (ICU).Results:The overall incidence of POD was 21%. S100-values on PD1 significantly predicted the occurrence of POD during the later hospital stay [area under the curve (AUC)=0.724 (95% confidence interval (CI): 0.619–0.814); p=0.0001] with an optimal cut-off level of 123 pg mLConclusions:S100-levels <123 pg mL


2019 ◽  
Author(s):  
Thomas Saller ◽  
Klaus F. Hofmann-Kiefer ◽  
Isabel Saller ◽  
Simon T. Schaefer ◽  
Bernhard Zwissler ◽  
...  

Abstract Background Postoperative delirium is associated with worse outcome. The aim of this study is to understand present strategies for delirium screening and therapy in German Post Anesthesia Caring Units (PACU) in hospitals and ambulatory anesthesia facilities. Methods We designed German-wide web-based survey of 922 leading anesthesiologists in hospitals and 726 in ambulatory surgery. Results The response rate was 30% for hospital anesthesiologists. 10% (95%-confidence interval: 8–12) of the anesthesiologists applied a standardised screening for delirium. Even though not on a regular basis, in 44% (41–47) of the hospitals, a recommended and validated screening was used, the Nursing Delirium Screening Scale (NuDesc) or the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). If delirium is likely to occur, 46% (43–50) of the patients were examined using a delirium tool and 20% (17–23) screened in intensive care units. For the treatment of delirium, alpha-2-agonists (83%, 80–85) were used most frequently for vegetative symptoms, benzodiazepines in anxiety in 71% (68–74), typical neuroleptics in 77% (71–82%) of patients with psychotic symptoms and in 20% (15–25) of patients with hypoactive delirium. 45% (39–51) of the respondents suggested no therapy for this entity. One third of the respondents indicated an age limit for pre-anesthetic medication with a mean age (SD) of 74.2 (±6.4) years and avoid benzodiazepines. Conclusions Monitoring of delirium was not established as a standard procedure in German PACUs. However, symptom-oriented therapy for postoperative delirium corresponded with the current guidelines.


2020 ◽  
Vol 132 (6) ◽  
pp. 1458-1468 ◽  
Author(s):  
Bradley A. Fritz ◽  
Christopher R. King ◽  
Arbi Ben Abdallah ◽  
Nan Lin ◽  
Angela M. Mickle ◽  
...  

Abstract Background Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium. Methods This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5. Results Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P &lt; 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation). Conclusions A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New


Author(s):  
Marwan Hamiko ◽  
Efstratios I. Charitos ◽  
Markus Velten ◽  
Tobias Hilbert ◽  
Christian Putensen ◽  
...  

Abstract Background Heart surgery with extracorporeal circulation (ECC) often leads to postoperative delirium (POD). This is associated with increased morbidity resulting in longer hospital stay and associated costs. The purpose of our study was to analyze the effect of intraoperative mannitol application on POD in patients undergoing elective aortic valve replacement (AVR). Materials and Methods In our retrospective single-center study, 259 patients underwent elective AVR, using Bretschneider cardioplegic solution for cardiac arrest, between 2014 and 2017. Patients were divided in mannitol (n = 188) and nonmannitol (n = 71) groups. POD was assessed using the confusion assessment method for the intensive care unit (ICU). Statistical significance was assumed at p < 0.05. Results Baseline patient characteristics did not differ between the groups. Incidence of POD was significantly higher in the nonmannitol group (33.8 vs. 13.8%; p = 0.001). These patients required longer ventilation time (24.1 vs. 17.1 hours; p = 0.021), higher reintubation rate (11.3 vs. 2.7%; p = 0.009), ICU readmission (12.7 vs. 4.8%; p = 0.026), prolonged ICU (112 vs. 70 hours; p = 0.040), and hospital stay (17.8 vs. 12.6 days; p < 0.001), leading to higher expenses (19,349 € vs. 16,606 €, p < 0.001). A 30-day mortality was not affected, but nonmannitol group showed higher Simplified Acute Physiology Score II score (32.2 vs. 28.7; p < 0.001). Mannitol substitution was independently associated with lower incidence of POD (odds ratio: 0.40; 95% confidence interval: 0.18–0.89; p = 0.02). Conclusion Treatment with mannitol during ECC was associated with decreased incidence of POD. This was accompanied by shorter ventilation time, ICU and hospital stay, and lower treatment expenses.


2020 ◽  
Vol 34 (5) ◽  
pp. 675-687
Author(s):  
Yan Zhang ◽  
Shu-Ting He ◽  
Bin Nie ◽  
Xue-Ying Li ◽  
Dong-Xin Wang

Abstract Background The clinical significance of emergence delirium remains unclear. The purpose of this study was to investigate the association between emergence delirium and postoperative delirium in elderly after general anesthesia and surgery. Methods This prospective observational study was done in a tertiary hospital in Beijing, China. Elderly patients (65–90 years) who underwent major noncardiac surgery under general anesthesia and admitted to the postanesthesia care unit (PACU) after surgery were enrolled. Emergence delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit during PACU stay. Postoperative delirium was assessed with the Confusion Assessment Method during the first 5 postoperative days. The association between emergence delirium and postoperative delirium was analyzed with a multivariable logistic regression model. Results A total of 942 patients were enrolled and 915 completed the study. Emergence delirium developed in 37.0% (339/915) of patients during PACU stay; and postoperative delirium developed in 11.4% (104/915) of patients within the first 5 postoperative days. After adjusted confounding factors, the occurrence of emergence delirium is independently associated with an increased risk of postoperative delirium (OR 1.717, 95% CI 1.078–2.735, P = 0.023). Patients with emergence delirium stayed longer in PACU and hospital after surgery, and developed more non-delirium complications within 30 days. Conclusions Emergence delirium in elderly admitted to the PACU after general anesthesia and major surgery is independently associated with an increased risk of postoperative delirium. Patients with emergence delirium had worse perioperative outcomes. Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR-OOC-17012734


2019 ◽  
Vol 131 (3) ◽  
pp. 492-500 ◽  
Author(s):  
Zhongyong Shi ◽  
Xinchun Mei ◽  
Cheng Li ◽  
Yupeng Chen ◽  
Hailin Zheng ◽  
...  

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Postoperative delirium is one of the most common complications in the elderly surgical population. However, its long-term outcomes remain largely to be determined. Therefore a prospective cohort study was conducted to determine the association between postoperative delirium and long-term decline in activities of daily living and postoperative mortality. The hypothesis in the present study was that postoperative delirium was associated with a greater decline in activities of daily living and higher mortality within 24 to 36 months after anesthesia and surgery. Methods The participants (at least 65 yr old) having the surgeries of (1) proximal femoral nail, (2) hip replacement, or (3) open reduction and internal fixation under general anesthesia were enrolled. The Confusion Assessment Method algorithm was administered to diagnose delirium before and on the first, second, and fourth days after the surgery. Activities of daily living were evaluated by using the Chinese version of the activities of daily living scale (range, 14 to 56 points), and preoperative cognitive function was assessed by using the Chinese Mini-Mental State Examination (range, 0 to 30 points). The follow-up assessments, including activities of daily living and mortality, were conducted between 24 and 36 months after anesthesia and surgery. Results Of 130 participants (80 ± 6 yr, 24% male), 34 (26%) developed postoperative delirium during the hospitalization. There were 32% of the participants who were lost to follow-up, resulting in 88 participants who were finally included in the data analysis. The participants with postoperative delirium had a greater decline in activities of daily living (16 ± 15 vs. 9 ± 15, P = 0.037) and higher 36-month mortality (8 of 28, 29% vs. 7 of 75, 9%; P = 0.009) as compared with the participants without postoperative delirium. Conclusions Postoperative delirium was associated with long-term detrimental outcomes, including greater decline in activities of daily living and a higher rate of postoperative mortality.


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